Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, American College of Rheumatology, High-sensitivity C-reactive protein, Bruton's tyrosine kinase
Brief summary
The purpose of this study was to determine the efficacy, dose response, and safety of M52951 in participants with Rheumatoid Arthritis (RA), and to consider a dose to took forward into Phase III development.
Interventions
DRUGM2591 25 mg QD
Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
DRUGM2951 75 mg QD
Participants received 75 mg of M2951 orally QD for 12 weeks.
DRUGM2951 50 mg BID
Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
DRUGPlacebo
Participants received placebo matched to M2951 orally for 12 weeks.
Sponsors
Merck KGaA, Darmstadt, Germany
EMD Serono Research & Development Institute, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* In Japan, if a participant is less than (\<) 20 years, the written informed consent from the participant's parent or guardian will be required in addition to the participant's written consent. * Confirmed diagnosis of RA according to 2010 ACR/EULAR RA classification criteria of at least 6 months duration prior to Screening * Persistently active moderate to severe RA at both Screening and Randomization (if significant surgical treatment of a joint has been performed, that joint cannot be counted for entry or enrollment purposes), as defined by: \>= 6 swollen joints (of 66 assessed) and \>= 6 tender joints (of 68 assessed). * An hsCRP \>= 5.0 milligram/liter (mg/L) at Screening * Treatment for \>= 16 weeks with 7.5 to 25 mg/week Methotrexate (MTX) at a stable dose and route of administration (oral or parenteral) for at least 8 weeks prior to dosing with the Investigational Medicinal Product (IMP) and maintained throughout the trial * For participants entering the trial on MTX doses \< 15 mg/week (\< 10 mg/week in Japan), there must be clear documentation in the medical record that higher doses of MTX were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines. * For MRI Sub-study participants, participants must have palpable synovitis of the wrist and/or \>= 1 of metacarpophalangeal joints 1 to 5, defined as loss of bony contours with palpable joint effusion and/or swelling, in the MRI-designated hand (that is., the hand being used in MRI assessments).
Exclusion criteria
* ACR functional class IV as defined by the ACR classification of functional status or wheelchair/bedbound * Use of oral corticosteroids greater than (\>) 10 mg daily prednisone equivalent, or change in dose of corticosteroids within 2 weeks prior to Screening or during Screening * Use of injectable corticosteroids (including intra-articular corticosteroids) or intra-articular hyaluronic acid within 4 weeks prior to Screening or during Screening * Initiation or change in dose for nonsteroidal anti-inflammatory drugs (NSAIDs) (including low-dose aspirin and cyclooxygenase-2 inhibitors) within 2 weeks prior to dosing with the IMP * High potency opioid analgesics are prohibited within 2 weeks prior to Screening and during the trial; other analgesics are allowed (that is, acetaminophen, codeine, hydrocodone\*, propoxyphene\*, or tramadol), although not within 24 hours of study visits with clinical assessments (\*not approved in Japan) * Current or prior treatment with any of the following: * Biologic Disease-modifying anti-rheumatic drugs (DMARDs) (approved or investigational), including but not limited to: * Tumor necrosis factor (TNF) antagonists or biosimilars of these agents (approved or investigational), or any investigational TNF antagonist * Interleukin-6 antagonists * Abatacept (CTLA4-Fc) * Anakinra\* (IL-1 receptor antagonist) (\*not approved in Japan) * B cell-depleting antibodies (example, rituximab, ocrelizumab\*, ofatumumab, obinutuzumab\*, ocaratuzumab\*, veltuzumab\*, or any biosimilars of these agents \[approved or investigational\]) (\*not approved in Japan) * Anti-BLyS (B lymphocyte stimulator) agents (example, belimumab, tabalumab\*) (\*not approved in Japan) * Dual BLyS/A proliferation-inducing ligand (APRIL) neutralizing agents (that is, atacicept\*, RCT-18\*) (\*not approved in Japan) * Targeted synthetic DMARDs, specifically: * Janus kinase inhibitors * Other Bruton's tyrosine kinase (BTK) inhibitors * Alkylating agents (example, chlorambucil\*, cyclophosphamide) (\*not approved in Japan). * The following restrictions on nonbiologic DMARD must be followed: * Auranofin (Ridaura), minocycline, penicillamine, sulfasalazine, cyclosporine, mycophenolate (mycophenolate sodium not approved in Japan), tacrolimus, azathioprine: must have been discontinued for 4 weeks prior to dosing with the IMP * Leflunomide (Arava) must have been discontinued 12 weeks prior to dosing with the IMP if no elimination procedure is followed. Alternately, it should have been discontinued with the following elimination procedure at least 4 weeks prior to dosing with the IMP: * Cholestyramine at a dosage of 8 gram 3 times a day for at least 24 hours, or activated charcoal at a dosage of 50 gram 4 times a day for at least 24 hours. * Injectable Gold (aurothioglucose\* or aurothiomalate): must have been discontinued for 8 weeks prior to dosing with the IMP (\*not approved in Japan) * Anti-malarials (hydroxychloroquine, chloroquine\*) will be allowed in this trial. Participants may be taking oral hydroxychloroquine (=\< 400 mg/day) or chloroquine (=\< 250 mg/day), doses must have been stable for at least 12 weeks prior to dosing with the IMP, and will need to be continued at that stable dose for the duration of the trial. If discontinued prior to this trial, they must have been discontinued for 4 weeks prior to dosing with the IMP (\*not approved in Japan). * For MRI Substudy: * Inability to comply with MRI scanning, including contraindications to MRI such as known allergy to gadolinium contrast media, claustrophobia (if the site does not have ability to scan extremities only), presence of a pacemaker, cochlear implants, ferromagnetic devices or clips, intracranial vascular clips, insulin pumps, and nerve stimulators. * More than 25% of applicable joints of the target hand and wrist having had prior surgery or showing maximum Genant-modified Sharp erosion (3.0) or joint-space narrowing (4.0) scores, based on single posteroanterior radiographs of target hand and wrist read centrally.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved American College of Rheumatology 20 Percent (%) Response Criteria (ACR20) Assessed Using High-Sensitivity C-reactive Protein (hsCRP) at Week 12 | Week 12 | ACR20 response: a participant has at least 20% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 20% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI); and 5) acute phase reactant as measured by high-sensitivity C-reactive protein (hsCRP). Percentage of participants with ACR20 response using hsCRP = Number of participants with ACR20 response using hsCRP divided by total modified intent-to-treat (mITT) participants \* 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Remission Disease Activity Score (DAS28 Less Than [<] 2.6) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12 | Week 12 | Disease Activity Score (DAS) based on a 28 joint count hsCRP consisted of composite numerical score of following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and participant's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP equals to (=) 0.56\*square root (sqrt) (TJC28) plus (+) 0.28\*sqrt (SJC28) + 0.36\*natural log(hsCRP+1) + 0.014\* participant's global assessment of disease activity + 0.96. Scores ranged 0-9.4, where lower scores indicated less disease activity. A DAS28 score less than (\<) 2.6 indicated clinical remission. Percentage of participants with low DAS28 \< 2.6 based on DAS28- hsCRP at Week 12 were reported. |
| Percentage of Participants Achieving American College of Rheumatology 50% Response Criteria (ACR50) | Week 12 | ACR50 response: a participant has at least 50% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 50% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire - Disability Index \[HAQ-DI\]; and 5) acute phase reactant as measured by High-sensitivity C-reactive protein \[hsCRP\]. Percentage of participants with ACR50 response = Number of participants with ACR50 response divided by total mITT participants \* 100. |
| Percentage of Participants Achieving American College of Rheumatology 70% Response Criteria (ACR70) | Week 12 | ACR70 response: a participant has at least 70% improvement ACR70 response in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 70% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire - Disability Index \[HAQ-DI\]; and 5) acute phase reactant as measured by High-sensitivity C-reactive protein \[hsCRP\]. Percentage of participants with ACR70 response = Number of participants with ACR70 response divided by total mITT participants \* 100. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | up to Week 16 | Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inparticipant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs: events between first dose of study drug that were absent before treatment/that worsened relative to pre-treatment state up to 16 weeks. TEAEs included both serious TEAEs and non-serious TEAEs. Number of participants with TEAEs and serious TEAEs were reported. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | up to Week 16 | Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1= Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs by severity were reported. |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | up to Week 16 | Vital signs included body temperature, systolic and diastolic blood pressure, pulse rate, respiratory rate, weight and height. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in vital signs were reported. |
| Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters | up to Week 16 | Laboratory investigation included hematology, biochemistry, urinalysis and coagulation. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in laboratory parameters were reported. |
| Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings | up to Week 16 | 12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. The corrected QT interval (QTcF) was calculated using Fridericia's formula. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semisupine position. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in 12-lead ECG findings were reported. |
| Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | Baseline, Week 2, 4, 8, 12 and 16 | Change in the serum levels of IgG, IgA, IgM were assessed. |
| Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Baseline, Week 2, 4, 8, 12 and 16 | Flow cytometry analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of B cell counts. |
| Percentage of Participants With Remission Assessed by American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean at Week 12 | Week 12 | ACR-EULAR Boolean remission was when a participant satisfied all of the following: tender joint count, swollen joint count (both based on a 28-joint assessment), C-reactive Protein (in milligrams per deciliter \[mg/dL\]), and participant's global assessment (visual analog scale \[VAS\]: 0 centimeter (cm) \[very well\] to 10 cm \[worst\], higher scores indicated worse health condition) and all scores were less than or equal to (\<=) 1. Percentage of participants with ACR-EULAR Boolean Remission were reported. |
| Percentage of Participants With Clinical Disease Activity Index (CDAI) Score Less Than or Equal to [=<] 2.8 at Week 12 | Week 12 | CDAI: a composite index (without acute-phase reactant) for assessing disease activity. The CDAI was calculated based on following formula: CDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PhGA where, GH = general health component of the Disease Activity Score \[DAS\] (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total CDAI score ranges from 0 to 76, where 0 (none) to 76 (extreme disease activity). CDAI score =\< 2.8 indicated clinical remission. Percentage of participants with CDAI score =\< 2.8 were reported. |
| Percentage of Participants With Simplified Disease Activity Index (SDAI) Score Less Than or Equal to [=<] 3.3 at Week 12 | Week 12 | SDAI was calculated based on following formula: SDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PGA + hsCRP where, GH = general health component of the Disease Activity Score \[DAS\] (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total SDAI score ranges from 0 to 86, where 0 (none) to 86 (extreme disease activity). SDAI score =\< 3.3 indicated clinical remission. Percentage of participants with SDAI score =\< 3.3 at Week 12 were reported. |
| Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Responses at Week 12 | Week 12 | EULAR Responder index based on 28 joint counts categorizes clinical response based on improvement since baseline in DAS28-CRP. DAS28-CRP scores range from 0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP \>5.1, low disease activity: DAS28-CRP \<3.2, and remission: DAS28-CRP \<2.6. EULAR DAS28-CRP responder index: good (absolute: \<3.2 or \>1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 improvement from baseline), or no response (absolute: \>5.1 or \<0.6 improvement from baseline). Percentage of Participants With Good or Moderate EULAR Responses were reported. |
| American College of Rheumatology (ACR) Hybrid Scores Computed Using High-Sensitivity C-reactive Protein (hsCRP) | Baseline, Week 12 | The hybrid ACR combines the ACR 20/50/70 response with the mean percent change in all 7 ACR core components, thus providing a percent improvement from baseline on a continuous scale. For each participant, the mean percent improvement from baseline across the 7 ACR core set measures (tender joint count, swollen joint count, Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity, disability index of the Health Assessment Questionnaire \[HAQ\], and C-reactive protein \[CRP\]) was calculated (a positive change indicated improvement, and the maximum worst change was limited to -100%) and the ACR20, ACR50, and ACR70 response is determined. The hybrid ACR is determined from a reference table taking into account both ACR response and mean percent improvement in the core set measures. Scores can range from -100% (maximal worsening) to 100% (maximal improvement). |
| Change From Baseline in Disease Activity Score (DAS) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12 | Baseline, Week 12 | DAS28 was a composite score used for measuring disease activity in participants with rheumatoid arthritis. The calculation was based on the tender joint count (out of 28 joints), swollen joint count (out of 28 joints), hsCRP (milligrams per liter \[mg/L\]) and Participant's Global Assessment of Disease Activity. Total DAS28-hsCRP score ranged from 0 (none) to 9.4 (extreme disease activity). DAS28-hsCRP \< 3.2 implied low disease activity and \>= 3.2 to \<= 5.1 implied moderate disease activity, \> 5.1 implied high disease activity. DAS28-hsCRP = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.36\*ln(hsCRP in mg/L +1) + 0.014\* Participant's Global Assessment of Disease Activity + 0.96; ln = natural logarithm, sqrt = square root. |
| Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 12 | Baseline, Week 12 | The CDAI was a composite index (without acute-phase reactant) for assessing disease activity. The CDAI was calculated based on following formula: CDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PhGA where, GH = general health component of the DAS (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total CDAI score ranges from 0 to 76, where 0 (none) to 76 (extreme disease activity). |
| Percentage of Participants With Low Disease Activity Score (DAS28 Less Than [<] 3.2) Based on 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12 | Week 12 | Disease Activity Score (DAS) based on a 28 joint count hsCRP consisted of composite numerical score of following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and participant's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP equals to (=) 0.56\*square root (sqrt) (TJC28) plus (+) 0.28\*sqrt (SJC28) + 0.36\*natural log(hsCRP+1) + 0.014\* participant's global assessment of disease activity + 0.96. Scores ranged 0-9.4, where lower scores indicated less disease activity. Percentage of participants with low DAS28 \< 3.2 based on DAS28- hsCRP at Week 12 were reported. |
| Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 | Baseline, Week 12 | Sixty-eight joints were assessed and classified as tender/not tender and Sixty-six joints were classified as swollen/not swollen by pressure and joint manipulation on physical examination. |
| Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12 | Baseline, Week 12 | The participant's overall assessment of disease activity was recorded using the 100 millimeter (mm) horizontal visual analog scale (VAS). The scale ranged from 0-100 mm, where 0 indicated no disease activity (symptom free and no arthritis symptoms) and 100 represented maximum disease activity (maximum arthritis disease activity). |
| Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12 | Baseline, Week 12 | The participants were asked to assess their level of pain by marking a vertical tick on a 100 mm horizontal VAS scale. The scale ranged from 0-100 mm, where 0 indicated no pain and 100 indicated worst possible pain. |
| Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12 | Baseline, Week 12 | HAQ-DI score was an evaluation of the functional status for a participant. The 20-question instrument assessed the degree of difficulty a person had in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0, indicated no difficulty, to 3, indicated inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty. |
| Percent Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12 | Baseline, Week 12 | The participants were asked to assess their level of pain by marking a vertical tick on a 100 mm horizontal VAS scale. The scale ranged from 0-100 mm, where 0 indicated no pain and 100 indicated worst possible pain. |
| Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12 | Baseline, Week 12 | The Physician's Global Assessment of Disease Activity was recorded using the 100 mm horizontal VAS. Physician rated participant's arthritis disease activity on a scale ranged from 0-100 mm, where 0 indicated no disease activity (no arthritis) and 100 represented maximum disease activity (maximum arthritis). |
| Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12 | Baseline, Week 12 | hsCRP was the American College of Rheumatology (ACR) Core Set measure of acute phase reactant. It was measured at the central laboratory to help assess the effect of M2951 on the participant's rheumatoid arthritis. |
| Percent Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 | Baseline, Week 12 | Sixty-eight joints were assessed and classified as tender/not tender and Sixty-six joints were classified as swollen/not swollen by pressure and joint manipulation on physical examination. |
| Percent Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12 | Baseline, Week 12 | The participant's overall assessment of disease activity was recorded using the 100 millimeter (mm) horizontal visual analog scale (VAS). The scale ranged from 0-100 mm, where 0 indicated no disease activity (symptom free and no arthritis symptoms) and 100 represented maximum disease activity (maximum arthritis disease activity). |
| Percent Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12 | Baseline, Week 12 | HAQ-DI score was an evaluation of the functional status for a participant. The 20-question instrument assessed the degree of difficulty a person had in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0, indicated no difficulty, to 3, indicated inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty. |
| Percent Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12 | Baseline, Week 12 | The Physician's Global Assessment of Disease Activity was recorded using the 100 mm horizontal VAS. Physician rated participant's arthritis disease activity on a scale ranged from 0-100 mm, where 0 indicated no disease activity (no arthritis) and 100 represented maximum disease activity (maximum arthritis). |
| Percent Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12 | Baseline, Week 12 | hsCRP was the American College of Rheumatology (ACR) Core Set measure of acute phase reactant. It was measured at the central laboratory to help assess the effect of M2951 on the participant's rheumatoid arthritis. |
| Change From Baseline in Synovitis Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12 | Baseline, Week 12 | A total of 8 joints in the hand and wrist were evaluated for RAMRIS synovitis. Individual joint scores were assessed on a scale of 0 (no synovitis) to 3 (67 to 100 percent volume enhancement). The final synovitis score was the sum of the individual joint scores. The total score from 8 joints ranges from 0 to 24, with 0 implying normal (no synovitis) and 24 implying 67 to 100 percent volume enhancement. |
| Change From Baseline in Bone Marrow Edema (Osteitis) Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12 | Baseline, Week 12 | A total of 25 locations in the hand and wrist were evaluated for RAMRIS bone edema or osteitis. Individual location scores range from 0 (no edema) to 3 (67 to 100 percent involvement of original articular bone) based on the proportion of estimated originally non-eroded bone involved. The final bone edema or osteitis score is the sum of the individual location scores. The total score from the 25 locations ranges from 0 to 75, with 0 implying no bone edema or osteitis and 75 implying 67 to 100 percent involvement of original articular bone. |
| Change From Baseline in Physical Function Using Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 | Baseline, Week 12 | The HAQ-DI questionnaire assessed the participant's self-perception on the degree of difficulty \[0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)\] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. |
| Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score at Week 12 | Baseline, Week 12 | The 36-Item Short-Form Health Survey (SF-36) was a standardized survey evaluating 8 aspects of functional health and well-being. These eight subscales were summarized as relating to either physical health or mental health. Physical component summary (PCS) was based primarily on physical functioning, role-physical, bodily pain, and general health scales and mental component summary (MCS) encompasses vitality, social functioning, role-emotional, and mental health scales. Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0-100 (100 = highest level of mental functioning). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0-100 (100 = highest level of physical functioning). |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 12 | Baseline, Week 12 | The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assess self-reported fatigue and its impact upon daily activities and function. It uses a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse possible score) to 52 (best score). A higher score reflected an improvement in the participant's health status. |
| Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12 | Baseline, Week 12 | SDAI was numerical sum of 5 outcome parameters: 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PGA + hsCRP where, GH = general health component of the DAS (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total SDAI score ranges from 0 to 86, where 0 (none) to 86 (extreme disease activity). |
Countries
Argentina, Bulgaria, Chile, Colombia, Czechia, Mexico, Poland, Russia, Serbia, South Africa, Ukraine, United States
Participant flow
Pre-assignment details
A total of 933 participants with rheumatoid arthritis were screened. Out of which, 390 participants were randomized in ratio of 1:1:1:1 to 1 of the 4 treatment groups: Placebo; M2951 25 milligrams (mg) once daily (QD), M2951 75 mg QD and M2951 50 mg twice daily (BID).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matched to M2951 orally for 12 weeks. | 97 |
| M2951 25 mg QD Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks. | 98 |
| M2951 75 mg QD Participants received 75 mg of M2951 orally QD for 12 weeks. | 96 |
| M2951 50 mg BID Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks. | 99 |
| Total | 390 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 3 | 6 | 3 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 3 | 0 | 0 |
| Overall Study | Other | 5 | 5 | 5 | 3 |
| Overall Study | Protocol Violation | 1 | 2 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | M2951 25 mg QD | M2951 75 mg QD | M2951 50 mg BID | Total |
|---|---|---|---|---|---|
| Age, Continuous | 52.9 years STANDARD_DEVIATION 12.24 | 50.9 years STANDARD_DEVIATION 13.15 | 53.3 years STANDARD_DEVIATION 11.33 | 53.7 years STANDARD_DEVIATION 12.13 | 52.7 years STANDARD_DEVIATION 12.21 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 32 Participants | 33 Participants | 35 Participants | 38 Participants | 138 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 65 Participants | 65 Participants | 61 Participants | 61 Participants | 252 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 4 Participants | 2 Participants | 10 Participants |
| Race (NIH/OMB) White | 92 Participants | 94 Participants | 91 Participants | 97 Participants | 374 Participants |
| Sex: Female, Male Female | 77 Participants | 82 Participants | 76 Participants | 77 Participants | 312 Participants |
| Sex: Female, Male Male | 20 Participants | 16 Participants | 20 Participants | 22 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 97 | 0 / 98 | 0 / 96 | 0 / 99 |
| other Total, other adverse events | 11 / 97 | 13 / 98 | 8 / 96 | 17 / 99 |
| serious Total, serious adverse events | 2 / 97 | 2 / 98 | 2 / 96 | 1 / 99 |
Outcome results
Primary
Percentage of Participants Who Achieved American College of Rheumatology 20 Percent (%) Response Criteria (ACR20) Assessed Using High-Sensitivity C-reactive Protein (hsCRP) at Week 12
ACR20 response: a participant has at least 20% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 20% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI); and 5) acute phase reactant as measured by high-sensitivity C-reactive protein (hsCRP). Percentage of participants with ACR20 response using hsCRP = Number of participants with ACR20 response using hsCRP divided by total modified intent-to-treat (mITT) participants \* 100.
Time frame: Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of Investigational Medicinal Product (IMP) (M2951 or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved American College of Rheumatology 20 Percent (%) Response Criteria (ACR20) Assessed Using High-Sensitivity C-reactive Protein (hsCRP) at Week 12 | 49.5 percentage of participants |
| M2951 25 mg QD | Percentage of Participants Who Achieved American College of Rheumatology 20 Percent (%) Response Criteria (ACR20) Assessed Using High-Sensitivity C-reactive Protein (hsCRP) at Week 12 | 59.2 percentage of participants |
| M2951 75 mg QD | Percentage of Participants Who Achieved American College of Rheumatology 20 Percent (%) Response Criteria (ACR20) Assessed Using High-Sensitivity C-reactive Protein (hsCRP) at Week 12 | 51.0 percentage of participants |
| M2951 50 mg BID | Percentage of Participants Who Achieved American College of Rheumatology 20 Percent (%) Response Criteria (ACR20) Assessed Using High-Sensitivity C-reactive Protein (hsCRP) at Week 12 | 59.6 percentage of participants |
p-value: 0.174695% CI: [0.84, 2.61]Regression, Logistic
p-value: 0.828395% CI: [0.61, 1.87]Regression, Logistic
p-value: 0.129895% CI: [0.88, 2.74]Regression, Logistic
Secondary
American College of Rheumatology (ACR) Hybrid Scores Computed Using High-Sensitivity C-reactive Protein (hsCRP)
The hybrid ACR combines the ACR 20/50/70 response with the mean percent change in all 7 ACR core components, thus providing a percent improvement from baseline on a continuous scale. For each participant, the mean percent improvement from baseline across the 7 ACR core set measures (tender joint count, swollen joint count, Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity, disability index of the Health Assessment Questionnaire \[HAQ\], and C-reactive protein \[CRP\]) was calculated (a positive change indicated improvement, and the maximum worst change was limited to -100%) and the ACR20, ACR50, and ACR70 response is determined. The hybrid ACR is determined from a reference table taking into account both ACR response and mean percent improvement in the core set measures. Scores can range from -100% (maximal worsening) to 100% (maximal improvement).
Time frame: Baseline, Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | American College of Rheumatology (ACR) Hybrid Scores Computed Using High-Sensitivity C-reactive Protein (hsCRP) | 26.51 percent change | Standard Deviation 25.779 |
| M2951 25 mg QD | American College of Rheumatology (ACR) Hybrid Scores Computed Using High-Sensitivity C-reactive Protein (hsCRP) | 34.66 percent change | Standard Deviation 29.033 |
| M2951 75 mg QD | American College of Rheumatology (ACR) Hybrid Scores Computed Using High-Sensitivity C-reactive Protein (hsCRP) | 33.09 percent change | Standard Deviation 27.724 |
| M2951 50 mg BID | American College of Rheumatology (ACR) Hybrid Scores Computed Using High-Sensitivity C-reactive Protein (hsCRP) | 36.99 percent change | Standard Deviation 26.241 |
Secondary
Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16
Flow cytometry analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of B cell counts.
Time frame: Baseline, Week 2, 4, 8, 12 and 16
Population: SAF included all participants who received at least 1 dose of IMP (M2951 or placebo). Here, Overall Number of Participants Analyzed specifies those participants who were evaluable for this outcome measure and Number Analyzed signified those participants who were evaluable for the specified category at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Week 4 | -20 cells per microliter (cells/microliter) | Standard Deviation 115.7 |
| Placebo | Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Week 2 | -13 cells per microliter (cells/microliter) | Standard Deviation 111 |
| Placebo | Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Week 8 | -21 cells per microliter (cells/microliter) | Standard Deviation 87.5 |
| Placebo | Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Week 16 | -20 cells per microliter (cells/microliter) | Standard Deviation 121.9 |
| Placebo | Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Week 12 | -22 cells per microliter (cells/microliter) | Standard Deviation 136.4 |
| M2951 25 mg QD | Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Week 16 | -3 cells per microliter (cells/microliter) | Standard Deviation 108.5 |
| M2951 25 mg QD | Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Week 2 | 264 cells per microliter (cells/microliter) | Standard Deviation 1832.7 |
| M2951 25 mg QD | Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Week 4 | 71 cells per microliter (cells/microliter) | Standard Deviation 130.1 |
| M2951 25 mg QD | Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Week 8 | 35 cells per microliter (cells/microliter) | Standard Deviation 103.1 |
| M2951 25 mg QD | Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Week 12 | 41 cells per microliter (cells/microliter) | Standard Deviation 111.8 |
| M2951 75 mg QD | Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Week 4 | 66 cells per microliter (cells/microliter) | Standard Deviation 145.3 |
| M2951 75 mg QD | Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Week 8 | 56 cells per microliter (cells/microliter) | Standard Deviation 188.1 |
| M2951 75 mg QD | Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Week 12 | 51 cells per microliter (cells/microliter) | Standard Deviation 156.2 |
| M2951 75 mg QD | Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Week 2 | 161 cells per microliter (cells/microliter) | Standard Deviation 648.3 |
| M2951 75 mg QD | Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Week 16 | -40 cells per microliter (cells/microliter) | Standard Deviation 133.5 |
| M2951 50 mg BID | Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Week 4 | 93 cells per microliter (cells/microliter) | Standard Deviation 137.6 |
| M2951 50 mg BID | Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Week 12 | 54 cells per microliter (cells/microliter) | Standard Deviation 145 |
| M2951 50 mg BID | Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Week 8 | 59 cells per microliter (cells/microliter) | Standard Deviation 145.4 |
| M2951 50 mg BID | Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Week 2 | 74 cells per microliter (cells/microliter) | Standard Deviation 144.8 |
| M2951 50 mg BID | Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16 | Week 16 | -19 cells per microliter (cells/microliter) | Standard Deviation 235.6 |
Secondary
Change From Baseline in Bone Marrow Edema (Osteitis) Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12
A total of 25 locations in the hand and wrist were evaluated for RAMRIS bone edema or osteitis. Individual location scores range from 0 (no edema) to 3 (67 to 100 percent involvement of original articular bone) based on the proportion of estimated originally non-eroded bone involved. The final bone edema or osteitis score is the sum of the individual location scores. The total score from the 25 locations ranges from 0 to 75, with 0 implying no bone edema or osteitis and 75 implying 67 to 100 percent involvement of original articular bone.
Time frame: Baseline, Week 12
Population: The MRI analysis set included all randomized participants who have at least at least 1 pre-dose and 1 post-dose MRI assessment. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Bone Marrow Edema (Osteitis) Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12 | -1 units on a scale | Standard Deviation 5.8 |
| M2951 25 mg QD | Change From Baseline in Bone Marrow Edema (Osteitis) Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12 | 0 units on a scale | Standard Deviation 4.6 |
| M2951 75 mg QD | Change From Baseline in Bone Marrow Edema (Osteitis) Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12 | 0 units on a scale | Standard Deviation 5.4 |
| M2951 50 mg BID | Change From Baseline in Bone Marrow Edema (Osteitis) Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12 | 0 units on a scale | Standard Deviation 4 |
Secondary
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 12
The CDAI was a composite index (without acute-phase reactant) for assessing disease activity. The CDAI was calculated based on following formula: CDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PhGA where, GH = general health component of the DAS (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total CDAI score ranges from 0 to 76, where 0 (none) to 76 (extreme disease activity).
Time frame: Baseline, Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 12 | -16.9 units on a scale | Standard Deviation 13.09 |
| M2951 25 mg QD | Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 12 | -18.0 units on a scale | Standard Deviation 13 |
| M2951 75 mg QD | Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 12 | -18.9 units on a scale | Standard Deviation 14.33 |
| M2951 50 mg BID | Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 12 | -20.3 units on a scale | Standard Deviation 13.9 |
Secondary
Change From Baseline in Disease Activity Score (DAS) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12
DAS28 was a composite score used for measuring disease activity in participants with rheumatoid arthritis. The calculation was based on the tender joint count (out of 28 joints), swollen joint count (out of 28 joints), hsCRP (milligrams per liter \[mg/L\]) and Participant's Global Assessment of Disease Activity. Total DAS28-hsCRP score ranged from 0 (none) to 9.4 (extreme disease activity). DAS28-hsCRP \< 3.2 implied low disease activity and \>= 3.2 to \<= 5.1 implied moderate disease activity, \> 5.1 implied high disease activity. DAS28-hsCRP = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.36\*ln(hsCRP in mg/L +1) + 0.014\* Participant's Global Assessment of Disease Activity + 0.96; ln = natural logarithm, sqrt = square root.
Time frame: Baseline, Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Disease Activity Score (DAS) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12 | -1.21 units on a scale | Standard Deviation 1.048 |
| M2951 25 mg QD | Change From Baseline in Disease Activity Score (DAS) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12 | -1.45 units on a scale | Standard Deviation 1.23 |
| M2951 75 mg QD | Change From Baseline in Disease Activity Score (DAS) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12 | -1.62 units on a scale | Standard Deviation 1.257 |
| M2951 50 mg BID | Change From Baseline in Disease Activity Score (DAS) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12 | -1.75 units on a scale | Standard Deviation 1.229 |
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 12
The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assess self-reported fatigue and its impact upon daily activities and function. It uses a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse possible score) to 52 (best score). A higher score reflected an improvement in the participant's health status.
Time frame: Baseline, Week 12
Population: QoL analysis set included all randomized participants who have received at least 1 dose of IMP (M2951 or placebo) and had at least 1 Baseline and 1 post Baseline QoL assessment. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 12 | 9 units on a scale | Standard Deviation 11.4 |
| M2951 25 mg QD | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 12 | 10 units on a scale | Standard Deviation 9.4 |
| M2951 75 mg QD | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 12 | 9 units on a scale | Standard Deviation 9 |
| M2951 50 mg BID | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 12 | 8 units on a scale | Standard Deviation 10.7 |
Secondary
Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12
hsCRP was the American College of Rheumatology (ACR) Core Set measure of acute phase reactant. It was measured at the central laboratory to help assess the effect of M2951 on the participant's rheumatoid arthritis.
Time frame: Baseline, Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12 | -1.11 milligram per liter (mg/L) | Standard Deviation 25.925 |
| M2951 25 mg QD | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12 | -6.42 milligram per liter (mg/L) | Standard Deviation 23.28 |
| M2951 75 mg QD | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12 | -5.45 milligram per liter (mg/L) | Standard Deviation 28.807 |
| M2951 50 mg BID | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12 | -7.69 milligram per liter (mg/L) | Standard Deviation 23.007 |
Secondary
Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12
The participants were asked to assess their level of pain by marking a vertical tick on a 100 mm horizontal VAS scale. The scale ranged from 0-100 mm, where 0 indicated no pain and 100 indicated worst possible pain.
Time frame: Baseline, Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12 | -21 millimeter | Standard Deviation 24.7 |
| M2951 25 mg QD | Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12 | -24 millimeter | Standard Deviation 26.9 |
| M2951 75 mg QD | Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12 | -22 millimeter | Standard Deviation 24.7 |
| M2951 50 mg BID | Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12 | -25 millimeter | Standard Deviation 26.6 |
Secondary
Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12
The participant's overall assessment of disease activity was recorded using the 100 millimeter (mm) horizontal visual analog scale (VAS). The scale ranged from 0-100 mm, where 0 indicated no disease activity (symptom free and no arthritis symptoms) and 100 represented maximum disease activity (maximum arthritis disease activity).
Time frame: Baseline, Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12 | -20 millimeter (mm) | Standard Deviation 29.6 |
| M2951 25 mg QD | Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12 | -19 millimeter (mm) | Standard Deviation 27.9 |
| M2951 75 mg QD | Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12 | -17 millimeter (mm) | Standard Deviation 29.6 |
| M2951 50 mg BID | Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12 | -25 millimeter (mm) | Standard Deviation 25.7 |
Secondary
Change From Baseline in Physical Function Using Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12
The HAQ-DI questionnaire assessed the participant's self-perception on the degree of difficulty \[0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)\] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.
Time frame: Baseline, Week 12
Population: Quality of Life (QoL) Analysis Set: all randomized participants who have received at least 1 dose of IMP (M2951 or placebo) and had at least 1 Baseline and 1 post baseline QoL assessment. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Physical Function Using Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 | -0.41 units on a scale | Standard Deviation 0.543 |
| M2951 25 mg QD | Change From Baseline in Physical Function Using Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 | -0.61 units on a scale | Standard Deviation 0.637 |
| M2951 75 mg QD | Change From Baseline in Physical Function Using Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 | -0.45 units on a scale | Standard Deviation 0.657 |
| M2951 50 mg BID | Change From Baseline in Physical Function Using Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 | -0.53 units on a scale | Standard Deviation 0.631 |
Secondary
Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12
The Physician's Global Assessment of Disease Activity was recorded using the 100 mm horizontal VAS. Physician rated participant's arthritis disease activity on a scale ranged from 0-100 mm, where 0 indicated no disease activity (no arthritis) and 100 represented maximum disease activity (maximum arthritis).
Time frame: Baseline, Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12 | -29 millimeter | Standard Deviation 21.2 |
| M2951 25 mg QD | Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12 | -33 millimeter | Standard Deviation 26.5 |
| M2951 75 mg QD | Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12 | -34 millimeter | Standard Deviation 26.1 |
| M2951 50 mg BID | Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12 | -37 millimeter | Standard Deviation 25.3 |
Secondary
Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16
Change in the serum levels of IgG, IgA, IgM were assessed.
Time frame: Baseline, Week 2, 4, 8, 12 and 16
Population: The SAF included all participants who received at least 1 dose of IMP (M2951 or placebo). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure and Number Analyzed signified those participants who were evaluable for the specified category at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgG: Week 2 | -0.02 gram per liter (g/L) | Standard Deviation 1.083 |
| Placebo | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgM: Week 4 | -0.04 gram per liter (g/L) | Standard Deviation 0.199 |
| Placebo | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgA: Week 12 | 0.02 gram per liter (g/L) | Standard Deviation 0.373 |
| Placebo | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgG: Week 8 | 0.12 gram per liter (g/L) | Standard Deviation 1.513 |
| Placebo | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgA: Week 16 | 0.01 gram per liter (g/L) | Standard Deviation 0.466 |
| Placebo | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgM: Week 2 | -0.04 gram per liter (g/L) | Standard Deviation 0.198 |
| Placebo | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgG: Week 12 | 0.47 gram per liter (g/L) | Standard Deviation 1.617 |
| Placebo | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgG: Week 4 | -0.05 gram per liter (g/L) | Standard Deviation 1.465 |
| Placebo | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgM: Week 12 | -0.01 gram per liter (g/L) | Standard Deviation 0.265 |
| Placebo | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgG: Week 16 | 0.08 gram per liter (g/L) | Standard Deviation 1.829 |
| Placebo | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgA: Week 2 | -0.01 gram per liter (g/L) | Standard Deviation 0.253 |
| Placebo | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgM: Week 8 | -0.03 gram per liter (g/L) | Standard Deviation 0.31 |
| Placebo | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgA: Week 4 | -0.05 gram per liter (g/L) | Standard Deviation 0.326 |
| Placebo | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgM: Week 16 | -0.16 gram per liter (g/L) | Standard Deviation 0.776 |
| Placebo | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgA: Week 8 | -0.02 gram per liter (g/L) | Standard Deviation 0.346 |
| M2951 25 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgA: Week 8 | -0.16 gram per liter (g/L) | Standard Deviation 1.322 |
| M2951 25 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgM: Week 4 | -0.11 gram per liter (g/L) | Standard Deviation 0.224 |
| M2951 25 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgG: Week 16 | -0.14 gram per liter (g/L) | Standard Deviation 2.349 |
| M2951 25 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgA: Week 12 | 0.01 gram per liter (g/L) | Standard Deviation 0.444 |
| M2951 25 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgG: Week 4 | -0.15 gram per liter (g/L) | Standard Deviation 1.576 |
| M2951 25 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgM: Week 2 | -0.04 gram per liter (g/L) | Standard Deviation 0.183 |
| M2951 25 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgM: Week 8 | -0.20 gram per liter (g/L) | Standard Deviation 0.243 |
| M2951 25 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgA: Week 16 | 0.07 gram per liter (g/L) | Standard Deviation 0.465 |
| M2951 25 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgG: Week 8 | -0.28 gram per liter (g/L) | Standard Deviation 2.052 |
| M2951 25 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgA: Week 4 | -0.01 gram per liter (g/L) | Standard Deviation 0.359 |
| M2951 25 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgM: Week 16 | -0.12 gram per liter (g/L) | Standard Deviation 0.436 |
| M2951 25 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgM: Week 12 | -0.20 gram per liter (g/L) | Standard Deviation 0.309 |
| M2951 25 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgA: Week 2 | -0.15 gram per liter (g/L) | Standard Deviation 1.187 |
| M2951 25 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgG: Week 12 | -0.17 gram per liter (g/L) | Standard Deviation 2.08 |
| M2951 25 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgG: Week 2 | -0.07 gram per liter (g/L) | Standard Deviation 1.042 |
| M2951 75 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgA: Week 8 | -0.06 gram per liter (g/L) | Standard Deviation 0.373 |
| M2951 75 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgG: Week 2 | -0.21 gram per liter (g/L) | Standard Deviation 0.968 |
| M2951 75 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgG: Week 4 | -0.34 gram per liter (g/L) | Standard Deviation 1.254 |
| M2951 75 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgG: Week 8 | -0.37 gram per liter (g/L) | Standard Deviation 1.565 |
| M2951 75 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgG: Week 12 | -0.33 gram per liter (g/L) | Standard Deviation 1.493 |
| M2951 75 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgG: Week 16 | -0.14 gram per liter (g/L) | Standard Deviation 1.808 |
| M2951 75 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgA: Week 2 | 0.00 gram per liter (g/L) | Standard Deviation 0.242 |
| M2951 75 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgA: Week 4 | -0.05 gram per liter (g/L) | Standard Deviation 0.333 |
| M2951 75 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgA: Week 12 | -0.08 gram per liter (g/L) | Standard Deviation 0.388 |
| M2951 75 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgA: Week 16 | -0.11 gram per liter (g/L) | Standard Deviation 0.38 |
| M2951 75 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgM: Week 2 | -0.03 gram per liter (g/L) | Standard Deviation 0.281 |
| M2951 75 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgM: Week 4 | -0.11 gram per liter (g/L) | Standard Deviation 0.217 |
| M2951 75 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgM: Week 8 | -0.23 gram per liter (g/L) | Standard Deviation 0.327 |
| M2951 75 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgM: Week 12 | -0.25 gram per liter (g/L) | Standard Deviation 0.296 |
| M2951 75 mg QD | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgM: Week 16 | -0.22 gram per liter (g/L) | Standard Deviation 0.246 |
| M2951 50 mg BID | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgA: Week 4 | 0.02 gram per liter (g/L) | Standard Deviation 0.396 |
| M2951 50 mg BID | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgG: Week 4 | -0.17 gram per liter (g/L) | Standard Deviation 1.168 |
| M2951 50 mg BID | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgM: Week 4 | -0.05 gram per liter (g/L) | Standard Deviation 0.385 |
| M2951 50 mg BID | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgA: Week 2 | 0.03 gram per liter (g/L) | Standard Deviation 0.369 |
| M2951 50 mg BID | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgG: Week 16 | 0.06 gram per liter (g/L) | Standard Deviation 1.96 |
| M2951 50 mg BID | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgG: Week 2 | -0.09 gram per liter (g/L) | Standard Deviation 1.062 |
| M2951 50 mg BID | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgM: Week 8 | -0.10 gram per liter (g/L) | Standard Deviation 0.485 |
| M2951 50 mg BID | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgG: Week 12 | -0.23 gram per liter (g/L) | Standard Deviation 1.781 |
| M2951 50 mg BID | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgG: Week 8 | -0.35 gram per liter (g/L) | Standard Deviation 2.037 |
| M2951 50 mg BID | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgM: Week 16 | -0.12 gram per liter (g/L) | Standard Deviation 0.487 |
| M2951 50 mg BID | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgA: Week 16 | 0.05 gram per liter (g/L) | Standard Deviation 0.478 |
| M2951 50 mg BID | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgA: Week 12 | 0.05 gram per liter (g/L) | Standard Deviation 0.545 |
| M2951 50 mg BID | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgM: Week 12 | -0.17 gram per liter (g/L) | Standard Deviation 0.406 |
| M2951 50 mg BID | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgM: Week 2 | -0.01 gram per liter (g/L) | Standard Deviation 0.323 |
| M2951 50 mg BID | Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16 | IgA: Week 8 | 0.07 gram per liter (g/L) | Standard Deviation 0.567 |
Secondary
Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12
SDAI was numerical sum of 5 outcome parameters: 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PGA + hsCRP where, GH = general health component of the DAS (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total SDAI score ranges from 0 to 86, where 0 (none) to 86 (extreme disease activity).
Time frame: Baseline, Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12 | -17.000 units on a scale | Standard Deviation 13.5175 |
| M2951 25 mg QD | Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12 | -18.647 units on a scale | Standard Deviation 13.5957 |
| M2951 75 mg QD | Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12 | -19.404 units on a scale | Standard Deviation 14.1591 |
| M2951 50 mg BID | Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12 | -21.053 units on a scale | Standard Deviation 14.372 |
Secondary
Change From Baseline in Synovitis Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12
A total of 8 joints in the hand and wrist were evaluated for RAMRIS synovitis. Individual joint scores were assessed on a scale of 0 (no synovitis) to 3 (67 to 100 percent volume enhancement). The final synovitis score was the sum of the individual joint scores. The total score from 8 joints ranges from 0 to 24, with 0 implying normal (no synovitis) and 24 implying 67 to 100 percent volume enhancement.
Time frame: Baseline, Week 12
Population: The Magnetic Resonance Imaging (MRI) analysis set included all randomized participants who have at least at least 1 pre-dose and 1 post-dose MRI assessment. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Synovitis Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12 | 0 units on a scale | Standard Deviation 1.9 |
| M2951 25 mg QD | Change From Baseline in Synovitis Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12 | -1 units on a scale | Standard Deviation 2.5 |
| M2951 75 mg QD | Change From Baseline in Synovitis Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12 | -1 units on a scale | Standard Deviation 3.4 |
| M2951 50 mg BID | Change From Baseline in Synovitis Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12 | -1 units on a scale | Standard Deviation 2.4 |
Secondary
Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12
Sixty-eight joints were assessed and classified as tender/not tender and Sixty-six joints were classified as swollen/not swollen by pressure and joint manipulation on physical examination.
Time frame: Baseline, Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 | TJC | -11 joints | Standard Deviation 12 |
| Placebo | Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 | SJC | -7 joints | Standard Deviation 7.5 |
| M2951 25 mg QD | Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 | SJC | -8 joints | Standard Deviation 6.1 |
| M2951 25 mg QD | Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 | TJC | -11 joints | Standard Deviation 10.6 |
| M2951 75 mg QD | Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 | TJC | -13 joints | Standard Deviation 13.2 |
| M2951 75 mg QD | Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 | SJC | -8 joints | Standard Deviation 7.7 |
| M2951 50 mg BID | Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 | TJC | -12 joints | Standard Deviation 10.8 |
| M2951 50 mg BID | Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 | SJC | -8 joints | Standard Deviation 6.6 |
Secondary
Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score at Week 12
The 36-Item Short-Form Health Survey (SF-36) was a standardized survey evaluating 8 aspects of functional health and well-being. These eight subscales were summarized as relating to either physical health or mental health. Physical component summary (PCS) was based primarily on physical functioning, role-physical, bodily pain, and general health scales and mental component summary (MCS) encompasses vitality, social functioning, role-emotional, and mental health scales. Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0-100 (100 = highest level of mental functioning). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0-100 (100 = highest level of physical functioning).
Time frame: Baseline, Week 12
Population: QoL analysis set: all randomized participants who have received at least 1 dose of IMP (M2951 or placebo) and had at least 1 Baseline and 1 post baseline QoL assessment. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score at Week 12 | PCS | 5.9 units on a scale | Standard Deviation 7.1 |
| Placebo | Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score at Week 12 | MCS | 4.9 units on a scale | Standard Deviation 11.46 |
| M2951 25 mg QD | Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score at Week 12 | MCS | 5.7 units on a scale | Standard Deviation 8.41 |
| M2951 25 mg QD | Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score at Week 12 | PCS | 7.1 units on a scale | Standard Deviation 8.5 |
| M2951 75 mg QD | Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score at Week 12 | PCS | 6.4 units on a scale | Standard Deviation 8.5 |
| M2951 75 mg QD | Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score at Week 12 | MCS | 5.0 units on a scale | Standard Deviation 11.72 |
| M2951 50 mg BID | Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score at Week 12 | PCS | 7.1 units on a scale | Standard Deviation 8.28 |
| M2951 50 mg BID | Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score at Week 12 | MCS | 4.7 units on a scale | Standard Deviation 8.95 |
Secondary
Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12
HAQ-DI score was an evaluation of the functional status for a participant. The 20-question instrument assessed the degree of difficulty a person had in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0, indicated no difficulty, to 3, indicated inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Time frame: Baseline, Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12 | -0.38 units on a scale | Standard Deviation 0.567 |
| M2951 25 mg QD | Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12 | -0.58 units on a scale | Standard Deviation 0.662 |
| M2951 75 mg QD | Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12 | -0.40 units on a scale | Standard Deviation 0.658 |
| M2951 50 mg BID | Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12 | -0.52 units on a scale | Standard Deviation 0.616 |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Vital signs included body temperature, systolic and diastolic blood pressure, pulse rate, respiratory rate, weight and height. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in vital signs were reported.
Time frame: up to Week 16
Population: The SAF included all participants who received at least 1 dose of IMP (M2951 or placebo).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| M2951 25 mg QD | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| M2951 75 mg QD | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| M2951 50 mg BID | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings
12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. The corrected QT interval (QTcF) was calculated using Fridericia's formula. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semisupine position. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in 12-lead ECG findings were reported.
Time frame: up to Week 16
Population: The SAF included all participants who received at least 1 dose of IMP (M2951 or placebo).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
| M2951 25 mg QD | Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
| M2951 75 mg QD | Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
| M2951 50 mg BID | Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Laboratory investigation included hematology, biochemistry, urinalysis and coagulation. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in laboratory parameters were reported.
Time frame: up to Week 16
Population: The SAF included all participants who received at least 1 dose of IMP (M2951 or placebo).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters | 0 Participants |
| M2951 25 mg QD | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters | 0 Participants |
| M2951 75 mg QD | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters | 0 Participants |
| M2951 50 mg BID | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inparticipant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs: events between first dose of study drug that were absent before treatment/that worsened relative to pre-treatment state up to 16 weeks. TEAEs included both serious TEAEs and non-serious TEAEs. Number of participants with TEAEs and serious TEAEs were reported.
Time frame: up to Week 16
Population: The safety analysis set (SAF) included all participants who received at least 1 dose of IMP (M2951 or placebo).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | TEAEs | 44 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Serious TEAEs | 2 Participants |
| M2951 25 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Serious TEAEs | 2 Participants |
| M2951 25 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | TEAEs | 48 Participants |
| M2951 75 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | TEAEs | 48 Participants |
| M2951 75 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Serious TEAEs | 2 Participants |
| M2951 50 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | TEAEs | 50 Participants |
| M2951 50 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Serious TEAEs | 1 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1= Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs by severity were reported.
Time frame: up to Week 16
Population: The SAF included all participants who received at least 1 dose of IMP (M2951 or placebo).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 4 | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 2 | 19 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 5 | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 3 | 2 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 1 | 33 Participants |
| M2951 25 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 3 | 5 Participants |
| M2951 25 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 4 | 1 Participants |
| M2951 25 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 5 | 0 Participants |
| M2951 25 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 2 | 14 Participants |
| M2951 25 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 1 | 42 Participants |
| M2951 75 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 3 | 1 Participants |
| M2951 75 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 1 | 37 Participants |
| M2951 75 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 2 | 23 Participants |
| M2951 75 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 4 | 0 Participants |
| M2951 75 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 5 | 0 Participants |
| M2951 50 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 4 | 0 Participants |
| M2951 50 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 2 | 17 Participants |
| M2951 50 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 1 | 40 Participants |
| M2951 50 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 3 | 1 Participants |
| M2951 50 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 5 | 0 Participants |
Secondary
Percentage of Participants Achieving American College of Rheumatology 50% Response Criteria (ACR50)
ACR50 response: a participant has at least 50% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 50% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire - Disability Index \[HAQ-DI\]; and 5) acute phase reactant as measured by High-sensitivity C-reactive protein \[hsCRP\]. Percentage of participants with ACR50 response = Number of participants with ACR50 response divided by total mITT participants \* 100.
Time frame: Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving American College of Rheumatology 50% Response Criteria (ACR50) | 19.6 percentage of participants |
| M2951 25 mg QD | Percentage of Participants Achieving American College of Rheumatology 50% Response Criteria (ACR50) | 28.6 percentage of participants |
| M2951 75 mg QD | Percentage of Participants Achieving American College of Rheumatology 50% Response Criteria (ACR50) | 27.1 percentage of participants |
| M2951 50 mg BID | Percentage of Participants Achieving American College of Rheumatology 50% Response Criteria (ACR50) | 26.3 percentage of participants |
p-value: 0.141995% CI: [-0.03, 0.21]Cochran-Mantel-Haenszel
p-value: 0.220295% CI: [-0.05, 0.19]Cochran-Mantel-Haenszel
p-value: 0.232895% CI: [-0.05, 0.19]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving American College of Rheumatology 70% Response Criteria (ACR70)
ACR70 response: a participant has at least 70% improvement ACR70 response in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 70% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire - Disability Index \[HAQ-DI\]; and 5) acute phase reactant as measured by High-sensitivity C-reactive protein \[hsCRP\]. Percentage of participants with ACR70 response = Number of participants with ACR70 response divided by total mITT participants \* 100.
Time frame: Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving American College of Rheumatology 70% Response Criteria (ACR70) | 5.2 percentage of participants |
| M2951 25 mg QD | Percentage of Participants Achieving American College of Rheumatology 70% Response Criteria (ACR70) | 11.2 percentage of participants |
| M2951 75 mg QD | Percentage of Participants Achieving American College of Rheumatology 70% Response Criteria (ACR70) | 10.4 percentage of participants |
| M2951 50 mg BID | Percentage of Participants Achieving American College of Rheumatology 70% Response Criteria (ACR70) | 10.1 percentage of participants |
p-value: 0.123295% CI: [-0.02, 0.15]Cochran-Mantel-Haenszel
p-value: 0.172595% CI: [-0.03, 0.14]Cochran-Mantel-Haenszel
p-value: 0.179595% CI: [-0.03, 0.13]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Clinical Disease Activity Index (CDAI) Score Less Than or Equal to [=<] 2.8 at Week 12
CDAI: a composite index (without acute-phase reactant) for assessing disease activity. The CDAI was calculated based on following formula: CDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PhGA where, GH = general health component of the Disease Activity Score \[DAS\] (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total CDAI score ranges from 0 to 76, where 0 (none) to 76 (extreme disease activity). CDAI score =\< 2.8 indicated clinical remission. Percentage of participants with CDAI score =\< 2.8 were reported.
Time frame: Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Clinical Disease Activity Index (CDAI) Score Less Than or Equal to [=<] 2.8 at Week 12 | 1.0 percentage of participants |
| M2951 25 mg QD | Percentage of Participants With Clinical Disease Activity Index (CDAI) Score Less Than or Equal to [=<] 2.8 at Week 12 | 4.1 percentage of participants |
| M2951 75 mg QD | Percentage of Participants With Clinical Disease Activity Index (CDAI) Score Less Than or Equal to [=<] 2.8 at Week 12 | 6.3 percentage of participants |
| M2951 50 mg BID | Percentage of Participants With Clinical Disease Activity Index (CDAI) Score Less Than or Equal to [=<] 2.8 at Week 12 | 3.0 percentage of participants |
95% CI: [-0.02, 0.09]
95% CI: [0, 0.12]
95% CI: [-0.03, 0.08]
Secondary
Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Responses at Week 12
EULAR Responder index based on 28 joint counts categorizes clinical response based on improvement since baseline in DAS28-CRP. DAS28-CRP scores range from 0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP \>5.1, low disease activity: DAS28-CRP \<3.2, and remission: DAS28-CRP \<2.6. EULAR DAS28-CRP responder index: good (absolute: \<3.2 or \>1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 improvement from baseline), or no response (absolute: \>5.1 or \<0.6 improvement from baseline). Percentage of Participants With Good or Moderate EULAR Responses were reported.
Time frame: Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Responses at Week 12 | 54.6 percentage of participants |
| M2951 25 mg QD | Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Responses at Week 12 | 65.3 percentage of participants |
| M2951 75 mg QD | Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Responses at Week 12 | 66.7 percentage of participants |
| M2951 50 mg BID | Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Responses at Week 12 | 71.7 percentage of participants |
95% CI: [-0.03, 0.24]
95% CI: [-0.02, 0.25]
95% CI: [0.05, 0.31]
Secondary
Percentage of Participants With Low Disease Activity Score (DAS28 Less Than [<] 3.2) Based on 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12
Disease Activity Score (DAS) based on a 28 joint count hsCRP consisted of composite numerical score of following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and participant's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP equals to (=) 0.56\*square root (sqrt) (TJC28) plus (+) 0.28\*sqrt (SJC28) + 0.36\*natural log(hsCRP+1) + 0.014\* participant's global assessment of disease activity + 0.96. Scores ranged 0-9.4, where lower scores indicated less disease activity. Percentage of participants with low DAS28 \< 3.2 based on DAS28- hsCRP at Week 12 were reported.
Time frame: Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Low Disease Activity Score (DAS28 Less Than [<] 3.2) Based on 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12 | 7.2 percentage of participants |
| M2951 25 mg QD | Percentage of Participants With Low Disease Activity Score (DAS28 Less Than [<] 3.2) Based on 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12 | 20.4 percentage of participants |
| M2951 75 mg QD | Percentage of Participants With Low Disease Activity Score (DAS28 Less Than [<] 3.2) Based on 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12 | 24.0 percentage of participants |
| M2951 50 mg BID | Percentage of Participants With Low Disease Activity Score (DAS28 Less Than [<] 3.2) Based on 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12 | 20.2 percentage of participants |
p-value: 0.007795% CI: [0.04, 0.23]Cochran-Mantel-Haenszel
p-value: 0.001395% CI: [0.07, 0.27]Cochran-Mantel-Haenszel
p-value: 0.00895% CI: [0.04, 0.23]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Remission Assessed by American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean at Week 12
ACR-EULAR Boolean remission was when a participant satisfied all of the following: tender joint count, swollen joint count (both based on a 28-joint assessment), C-reactive Protein (in milligrams per deciliter \[mg/dL\]), and participant's global assessment (visual analog scale \[VAS\]: 0 centimeter (cm) \[very well\] to 10 cm \[worst\], higher scores indicated worse health condition) and all scores were less than or equal to (\<=) 1. Percentage of participants with ACR-EULAR Boolean Remission were reported.
Time frame: Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Remission Assessed by American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean at Week 12 | 0.0 percentage of participants |
| M2951 25 mg QD | Percentage of Participants With Remission Assessed by American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean at Week 12 | 0.0 percentage of participants |
| M2951 75 mg QD | Percentage of Participants With Remission Assessed by American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean at Week 12 | 1.0 percentage of participants |
| M2951 50 mg BID | Percentage of Participants With Remission Assessed by American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean at Week 12 | 3.0 percentage of participants |
95% CI: [-0.04, 0.04]
95% CI: [-0.03, 0.06]
95% CI: [-0.01, 0.09]
Secondary
Percentage of Participants With Remission Disease Activity Score (DAS28 Less Than [<] 2.6) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12
Disease Activity Score (DAS) based on a 28 joint count hsCRP consisted of composite numerical score of following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and participant's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP equals to (=) 0.56\*square root (sqrt) (TJC28) plus (+) 0.28\*sqrt (SJC28) + 0.36\*natural log(hsCRP+1) + 0.014\* participant's global assessment of disease activity + 0.96. Scores ranged 0-9.4, where lower scores indicated less disease activity. A DAS28 score less than (\<) 2.6 indicated clinical remission. Percentage of participants with low DAS28 \< 2.6 based on DAS28- hsCRP at Week 12 were reported.
Time frame: Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Remission Disease Activity Score (DAS28 Less Than [<] 2.6) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12 | 1.0 percentage of participants |
| M2951 25 mg QD | Percentage of Participants With Remission Disease Activity Score (DAS28 Less Than [<] 2.6) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12 | 10.2 percentage of participants |
| M2951 75 mg QD | Percentage of Participants With Remission Disease Activity Score (DAS28 Less Than [<] 2.6) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12 | 10.4 percentage of participants |
| M2951 50 mg BID | Percentage of Participants With Remission Disease Activity Score (DAS28 Less Than [<] 2.6) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12 | 10.1 percentage of participants |
p-value: 0.005695% CI: [0.03, 0.17]Cochran-Mantel-Haenszel
p-value: 0.00595% CI: [0.03, 0.17]Cochran-Mantel-Haenszel
p-value: 0.005395% CI: [0.03, 0.17]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Simplified Disease Activity Index (SDAI) Score Less Than or Equal to [=<] 3.3 at Week 12
SDAI was calculated based on following formula: SDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PGA + hsCRP where, GH = general health component of the Disease Activity Score \[DAS\] (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total SDAI score ranges from 0 to 86, where 0 (none) to 86 (extreme disease activity). SDAI score =\< 3.3 indicated clinical remission. Percentage of participants with SDAI score =\< 3.3 at Week 12 were reported.
Time frame: Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Simplified Disease Activity Index (SDAI) Score Less Than or Equal to [=<] 3.3 at Week 12 | 0.0 percentage of participants |
| M2951 25 mg QD | Percentage of Participants With Simplified Disease Activity Index (SDAI) Score Less Than or Equal to [=<] 3.3 at Week 12 | 3.1 percentage of participants |
| M2951 75 mg QD | Percentage of Participants With Simplified Disease Activity Index (SDAI) Score Less Than or Equal to [=<] 3.3 at Week 12 | 4.2 percentage of participants |
| M2951 50 mg BID | Percentage of Participants With Simplified Disease Activity Index (SDAI) Score Less Than or Equal to [=<] 3.3 at Week 12 | 3.0 percentage of participants |
95% CI: [-0.01, 0.09]
95% CI: [0, 0.1]
95% CI: [-0.01, 0.09]
Secondary
Percent Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12
HAQ-DI score was an evaluation of the functional status for a participant. The 20-question instrument assessed the degree of difficulty a person had in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0, indicated no difficulty, to 3, indicated inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Time frame: Baseline, Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12 | -20.09 percent change | Standard Deviation 40.084 |
| M2951 25 mg QD | Percent Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12 | -31.85 percent change | Standard Deviation 37.124 |
| M2951 75 mg QD | Percent Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12 | -21.27 percent change | Standard Deviation 44.571 |
| M2951 50 mg BID | Percent Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12 | -27.12 percent change | Standard Deviation 42.624 |
Secondary
Percent Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12
hsCRP was the American College of Rheumatology (ACR) Core Set measure of acute phase reactant. It was measured at the central laboratory to help assess the effect of M2951 on the participant's rheumatoid arthritis.
Time frame: Baseline, Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12 | 95.01 percent change | Standard Deviation 380.161 |
| M2951 25 mg QD | Percent Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12 | 10.93 percent change | Standard Deviation 167.257 |
| M2951 75 mg QD | Percent Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12 | 182.57 percent change | Standard Deviation 1775.154 |
| M2951 50 mg BID | Percent Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12 | -13.91 percent change | Standard Deviation 105.688 |
Secondary
Percent Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12
The participants were asked to assess their level of pain by marking a vertical tick on a 100 mm horizontal VAS scale. The scale ranged from 0-100 mm, where 0 indicated no pain and 100 indicated worst possible pain.
Time frame: Baseline, Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12 | -23 percent change | Standard Deviation 65 |
| M2951 25 mg QD | Percent Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12 | -32 percent change | Standard Deviation 38.4 |
| M2951 75 mg QD | Percent Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12 | -29 percent change | Standard Deviation 40.5 |
| M2951 50 mg BID | Percent Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12 | -32 percent change | Standard Deviation 48.4 |
Secondary
Percent Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12
The participant's overall assessment of disease activity was recorded using the 100 millimeter (mm) horizontal visual analog scale (VAS). The scale ranged from 0-100 mm, where 0 indicated no disease activity (symptom free and no arthritis symptoms) and 100 represented maximum disease activity (maximum arthritis disease activity).
Time frame: Baseline, Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12 | -13 percent change | Standard Deviation 111 |
| M2951 25 mg QD | Percent Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12 | -21 percent change | Standard Deviation 69.3 |
| M2951 75 mg QD | Percent Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12 | -13 percent change | Standard Deviation 65.7 |
| M2951 50 mg BID | Percent Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12 | -33 percent change | Standard Deviation 35.9 |
Secondary
Percent Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12
The Physician's Global Assessment of Disease Activity was recorded using the 100 mm horizontal VAS. Physician rated participant's arthritis disease activity on a scale ranged from 0-100 mm, where 0 indicated no disease activity (no arthritis) and 100 represented maximum disease activity (maximum arthritis).
Time frame: Baseline, Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12 | -42 percent change | Standard Deviation 31.4 |
| M2951 25 mg QD | Percent Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12 | -44 percent change | Standard Deviation 51.9 |
| M2951 75 mg QD | Percent Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12 | -47 percent change | Standard Deviation 34.9 |
| M2951 50 mg BID | Percent Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12 | -52 percent change | Standard Deviation 33.5 |
Secondary
Percent Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12
Sixty-eight joints were assessed and classified as tender/not tender and Sixty-six joints were classified as swollen/not swollen by pressure and joint manipulation on physical examination.
Time frame: Baseline, Week 12
Population: The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 | TJC | -39 percent change | Standard Deviation 45.6 |
| Placebo | Percent Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 | SJC | -46 percent change | Standard Deviation 52.7 |
| M2951 25 mg QD | Percent Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 | SJC | -53 percent change | Standard Deviation 42.6 |
| M2951 25 mg QD | Percent Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 | TJC | -46 percent change | Standard Deviation 44.2 |
| M2951 75 mg QD | Percent Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 | TJC | -51 percent change | Standard Deviation 42.8 |
| M2951 75 mg QD | Percent Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 | SJC | -56 percent change | Standard Deviation 40.3 |
| M2951 50 mg BID | Percent Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 | TJC | -49 percent change | Standard Deviation 37.5 |
| M2951 50 mg BID | Percent Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 | SJC | -58 percent change | Standard Deviation 43.8 |